Methods for preparing pyrimidine nucleoside-derived organopalladium and organonickel intermediates will be developed. Two routes to be investigated include the exchange reaction between Pd(II) and pyrimidine nucleosides covalently mercurated at the C-5 position, and oxidative addition of Pd(0) and Ni(0) complexes to pyrimidine nucleosides substituted by bromine or iodine at C-5. Reactions between a wide variety of substituted alkenes and the nucleoside-derived organopalladium and organonickel intermediates will be investigated as a means to introduce carbon chains into the C-5 position of pyrimidine nucleosides. The C-5 substituted pryimidine nucleosides derived from 2'-deoxyuridine so obtained are of interest as potential thymidine antagonists, and as antiviral and antitumor agents. The reaction between terminal acetylenes and the nucleoside-derived organotransition metal intermediates will be investigated with the synthesis of 2'-deoxy-5-ethynyluridine a prime goal. The preparation of nucleotide and polynucleotide-derived orgnopalladium and organonickel intermediates will be pursued with efforts directed toward development of methods suitable for modifying, with a high degree of specificity, the pyrimidine C-5 position in natural DNA and RNA. A synthetic route to polycytidylic acid substituted at the C-5 position by aminoalkyl groups will be developed. The copolymer with polyinosinic acid would be a potentially potent interferon inducer. All new compounds will be tested for antiviral and antitumor activity.